Evodiamine Eliminates Colon Cancer Stem Cells via Suppressing Notch and Wnt Signaling

Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2019-12, Vol.24 (24), p.4520
Main Authors: Kim, Hyejin, Yu, Yeongji, Choi, SeokGyeong, Lee, Hani, Yu, Jinsuh, Lee, Jeong-Ho, Kim, Woo-Young
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis
Biotechnology
Breast cancer
Cancer therapies
Cell cycle
Cell Cycle - drug effects
Cell death
Cell Line, Tumor
Cell lines
Cell Proliferation - drug effects
Colon
Colon cancer
Colorectal cancer
Dose-Response Relationship, Drug
Drug dosages
Humans
Medical prognosis
Metastasis
Mortality
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Population
Quinazolines - pharmacology
Receptors, Notch - metabolism
Signal transduction
Signal Transduction - drug effects
Stem cells
Toxicity
Wnt protein
Wnt Proteins - metabolism
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Summary:Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines' BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines' CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24244520